Highly effective neuroleptic drugs have been available for the past 40 years, but 50% of schizophrenic patients, under normal treatment conditions, relapse within 1 year after their latest episode, frequently spending 15-20% of their time in psychiatric institutions. The term relapse usually refers to a deterioration or recurrence of positive rather than negative features, and relapses appear to impair the course of the disease. Impairment is often longer than expected for those patients who discontinue antipsychotic medication and then relapse to their prediscontinuation clinical state of function. Drug therapy is an important defense against relapse. Marked differences in relapse rate between patients receiving placebo and neuroleptic drugs have been observed (approximately 69% after 1 year for the placebo group versus 26% for the neuroleptic group). First-year relapse rates can be reduced from 75% to 15% with prophylactic treatment with neuroleptics. Follow-up studies suggest that noncompliance with medication, pharmacological factors, psychosocial factors and alcohol and drug abuse contribute to setting off new psychotic episodes. The most important of these is noncompliance with medication. The overwhelming majority of schizophrenic patients who suffered a clinical exacerbation and required hospitalization (73%) did not comply with the treatment prescribed. The effect of new antipsychotic agents should be examined in patients who relapse despite maintenance treatment with conventional neuroleptics. We have found that the rate of current drug abuse among patients with schizophrenic relapse (44%) was significantly higher than that in schizophrenic patients who regularly attended outpatient clinics. Also, the rate of alcohol and substance abuse is higher in males (79%) than in females (21%). Psychiatric units should integrate addiction treatments with psychotic-relapse management.